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Comparative biodistribution of potential anti-glioblastoma conjugates [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF in normal mice
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences. (Biomedicinsk strålningsvetenskap)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences. (Biomedicinsk strålningsvetenskapBiomedicinsk strålningsvetenskap)ORCID iD: 0000-0001-6120-2683
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences. (Biomedicinsk strålningsvetenskap)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Biomedical Radiation Sciences. (Biomedicinsk strålningsvetenskap)
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2004 (English)In: Cancer Biotherapy and Radiopharmaceuticals, ISSN 1084-9785, E-ISSN 1557-8852, Vol. 19, no 4, 491-501 p.Article in journal (Refereed) Published
Abstract [en]

EGF-receptors (EGFR) are overexpressed in gliomas, as well as in tumors of breast, lung, and urinary bladder. For this reason, EGFR may be an attractive target for both visualization and therapy of malignant tumors using radioactive nuclides. Natural ligand of EGFR, epidermal growth factor (EGF) is a small 53-amino-acid protein. Low molecular weight of EGF may enable better intratumoral penetration in comparison to antibodies. [111In]DTPA-EGF was proposed for the targeting of glioblastoma and breast cancer, and its tumor-seeking properties were confirmed in animal studies. The aim of this study was to evaluate how the substitution of heptadentate DTPA for octadentate benzyl-DTPA (Bz-DTPA) effects the biodistribution of indium-labeled human EGF (hEGF) in normal NMRI mice. [111In]DTPA-hEGF and [111In]Bz-DTPA-hEGF, obtained by the coupling of ITC-benzyl-DTPA to hEGF, were injected into the tail vein. At 0.5, 1, 4, and 24 hours postinjection, the animals were sacrificed, and radioactivity in different organs was measured. The blood clearance of both conjugates was fast. The uptake of both conjugates in the liver, spleen, stomach, pancreas, intestines, and submaxillary gland was most likely receptor-mediated. The uptake in a majority of organs was similar. However, indium uptake in the case of [111In]DTPA-hEGF was significantly higher in the kidneys and bones. In conclusion, [111In]Bz-DTPA-hEGF seems to have more favourable in vivo distribution in comparison to [111In]DTPA-hEGF.

Place, publisher, year, edition, pages
2004. Vol. 19, no 4, 491-501 p.
Keyword [en]
Animals, Comparative Study, Epidermal Growth Factor/*pharmacokinetics, Female, Glioblastoma/*radiotherapy, Indium Radioisotopes/*pharmacokinetics, Isothiocyanates/*pharmacokinetics, Mice, Pentetic Acid/*analogs & derivatives/*pharmacokinetics, Radiopharmaceuticals/*pharmacokinetics, Receptor; Epidermal Growth Factor/metabolism, Research Support; Non-U.S. Gov't
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Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-72868DOI: 10.1089/cbr.2004.19.491PubMedID: 15453964OAI: oai:DiVA.org:uu-72868DiVA: diva2:100779
Available from: 2007-02-12 Created: 2007-02-12 Last updated: 2015-03-24Bibliographically approved

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Tolmachev, VladimirOrlova, AnnaCarlsson, Jörgen

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